1. Field of the Invention
The current invention relates to vessel covers, and more specifically but not exclusively, to covers for dissolution-testing vessels and the like.
2. Description of the Related Art
Dissolution testing is an important part of the process of drug discovery and pharmaceutical quality control. Dissolution testing is used to determine the rate at which a substance dissolves in a solvent. For example, dissolution testing may be used to determine the dissolution rate of a pharmaceutical product in a solution simulating, in chemical composition and temperature, fluids of the human digestive tract. Determination of the dissolution rate of pharmaceutical dosage indicates the potential availability of the pharmaceutical for absorption by patients. The dissolution rate, together with information about, for example, the solubility, permeability, and pharmacokinetics of a pharmaceutical, may be used to determine the pharmaceutical's in-vivo availability (also referred to as bioavailability). Dissolution testing may also be used to verify uniformity among production lots of a pharmaceutical. In order to allow comparison of results obtained by different apparatuses and/or at different times, standardized testing parameters are useful. A particular set of dissolution-testing parameters used for a particular test is commonly referred to as a method.
The United States Pharmacopeia (USP) is a non-governmental, official, public, standards-setting authority for prescription and over-the-counter medicines and other healthcare products manufactured or sold in the United States. The USP defines that a covered vessel must be used for pharmaceutical dissolution testing, where the vessel is made of glass or other inert transparent material. The materials should not absorb, react, or interfere with the specimen being tested. A vessel cover should be designed to prevent contamination from entering the test sample (both particle and gas) and prevent evaporative losses.
FIG. 1 shows a simplified perspective view of exemplary module 100 that is part of a conventional dissolution testing apparatus (not shown). Module 100 comprises glass vessel 101, which contains pharmaceutical 102 in solution 103, whose top surface is indicated by meniscus 104. Stirring paddle 105 is shown inside solution 103. Stirring paddle 105 is connected to and rotated by stirring shaft 106. At the top of vessel 101 is opening 107. Solution 103 is kept at a desired testing temperature, such as 37° Celsius, by means such as a water bath (not shown) or heating sleeves (not shown). At room temperature and pressure, solution 103 may experience significant evaporative loss over time if opening 107 is not covered.
FIGS. 2(A) and 2(B) show simplified top views of exemplary, conventional vessel covers 200 and 201, which are designed to cover and close opening 107 of FIG. 1. Covers 200 and 201 are made of acrylic or a similar hard plastic. Covers 200 and 201 have central openings 202 and 203, respectively, for stirring shaft 106. Covers 200 and 201 further comprise slots 204 and 205, respectively, to allow covers 200 and 201, respectively, to be placed on and/or removed from opening 107 while stirring shaft 106 is positioned in vessel 101 such that paddle 105 is inside solution 103. Cover 201 also has peripheral opening 206 and second slot 207 to allow insertion or removal of materials from vessel 101, while cover 201 remains on opening 107. The additional opening and slot of cover 201 permit, for example, (1) the use of a probe to add and/or remove samples of solution 103 and (2) the introduction of additional pharmaceuticals, without the removal of cover 201 from opening 107. However, slots 204 and 205 of covers 200 and 201, respectively, are fairly large and may allow for greater-than-desired evaporative losses or contamination potential.
FIG. 3 shows a simplified perspective view of conventional probe 300. Probe 300 comprises cannula 301, which connects to hub 302, which, in turn, connects to barrel 303. At the distal end of cannula 301 away from hub 302 is inlet 304. Note that inlet 304 may be used as either an inlet or outlet and is called an inlet herein because the more-common use of probe 300 is to extract samples of solution 103. Probe 300 may also be used, for example, to add to solution 103. The diameter of barrel 303 is larger than the diameter of hub 302 and the diameter of hub 302 is larger than the diameter of cannula 301. Barrel 303 and/or hub 302 may contain a filter (not shown) for preventing certain material from passing through probe 300.
FIG. 4 shows a simplified top view of exemplary, conventional, multi-piece vessel cover 400, designed to cover and close opening 107 of FIG. 1. Vessel cover 400 comprises first half-cover 401 and second half-cover 402, held together by hinge 403, where half-covers 401 and 402 are made of acrylic or similar rigid plastic. Hinge 403 allows half-covers 401 and 402 to swing relative to each other, as though folding vessel cover 400 approximately about the central diameter that separates half-covers 401 and 402. This folding splits apart half-covers 401 and 402 allowing the folded vessel cover 400 to be placed around stirring shaft 106. Then half-covers 401 and 402 may be brought together to form a flat disk with stirring shaft 106 in central opening 404. Half-covers 401 and 402 include peripheral openings 405 and 406, respectively, for the use of a probe or introduction of pharmaceuticals, as described above. Peripheral openings 405 and 406 may be closed with plugs (not shown) when not in use to reduce evaporative losses and contamination potential.
FIG. 5 shows a simplified top view of vessel cover 500, which is substantially similar to vessel cover 400 of FIG. 4, but with only one peripheral opening, opening 501, which corresponds to peripheral opening 405 of vessel cover 400. Peripheral opening 501 is covered with valve 502, which is made of a flexible material, such as rubber. Valve 502 is semi-permanently attached to cover 500 by tabs 504 and 505, which are attached to cover 500 by screws (not shown) or similar fasteners. Central portion 503 of valve 502 is sliced to form flaps allowing probes and pharmaceuticals to be inserted through valve 502 and peripheral opening 501. After a probe or other item is removed from valve 502, the flaps of central portion 503 are supposed to return to their original position.
FIG. 6 shows a simplified top view of exemplary, conventional, multi-piece vessel cover 600, designed to cover and close opening 107 of FIG. 1. Vessel cover 600 comprises concentric disks 601 and 602, which are attached together by rotational hinge 603 that allows disk 602 to rotate relative to disk 601. Both disks 601 and 602 have central opening 604 for stirring shaft 106. Both disks 601 and 602 are made from a rigid plastic. Disk 601 comprises peripheral openings 605 and 606 and slot 607, which are designed to function in the ways described above for peripheral openings and slots. Disk 602 includes slot 608, which is also designed to function in the way described above for slots. Disk 602 is shown as located below disk 601, where the portions of disk 602 visible through openings 605 and 606 and slot 607 are shown as striped. FIG. 6 shows disks 601 and 602 aligned so that slot 607 and openings 605 and 606 of disk 601 are occluded by disk 602. This alignment of the disks is useful for when cover 600 is in place over opening 107. Disks 602 and/or 601 may be rotated relative to each other so that slot 608 of disk 602 aligns with any one of opening 605, slot 607, and opening 606. If slot 608 is aligned with slot 607, then cover 600 may be fitted around, or removed from around, stirring shaft 106. When slot 608 is aligned with a peripheral opening, such as opening 605 or 606, then the peripheral opening may be used as described above.
FIG. 7 shows exemplary dissolution-testing module 700, which is a modification of module 100 of FIG. 1, where paddle 105 has been replaced with basket 701, stirring shaft 106 has been replaced by stirring shaft 702, and where pharmaceutical 102 is placed inside basket 701. Note that, in some systems, stirring shaft 702 may be substantially identical to stirring shaft 106, while, in other systems, stirring shaft 702 is substantially different from stirring shaft 106. Basket 701 is substantially a cylinder having a mesh wall, where the basket may be opened for the insertion of pharmaceutical samples such as pharmaceutical 102. A typical dissolution-testing basket has a removable top cap and a tight-weave mesh side wall and bottom. Other elements of module 700 are substantially the same as in module 100 and are labeled similarly. In some circumstances, it may be desired to raise or lower basket 701 while a vessel cover is in place over opening 107. Several conventional vessel covers have been described where the central opening of the covers is of a diameter appropriate to surround a stirring shaft, such as stirring shaft 106 of FIG. 1 or stirring shaft 702 of FIG. 7. Similar vessel covers may have a larger central opening that is large enough to accommodate the diameter of basket 701.
FIG. 8 shows a simplified top view of exemplary, conventional large-central-opening vessel cover 800. Cover 800 is substantially the same as cover 400 of FIG. 4, except that central opening 801 is larger than opening 404 of cover 400. In particular, central opening 801 has a diameter larger than, though similar to, the diameter of basket 701. In order to reduce evaporation losses and contamination probability because of the large central opening, a cap plug may be used in conjunction with basket 701 and vessel cover 800.
FIG. 9 shows a simplified bottom perspective view of cap plug 900, which may be used in conjunction with module 700 of FIG. 7 and vessel cover 800 of FIG. 8. Cap plug 900 is made of a rigid plastic and comprises lower disk 901 and upper disc 902. In the center of lower disk 901 is central opening 903. Upper disk 902 has a central opening whose diameter is at least as large as the diameter of central opening 903. The diameter of central opening 903 is similar to, though larger than, the diameters of stirring shafts 106 and 702 of FIG. 1 and FIG. 7, respectively. The outer diameter of lower disk 901 is similar to, though smaller than, the diameter of central opening 801 of vessel cover 800. The outer diameter of upper disk 902 is sufficiently larger than the diameter of central opening 801 so as to not be able to go through central opening 801.
Cap plug 900 may be slipped on the stirring shaft 702 of FIG. 7 when nothing is attached to the top or bottom of stirring shaft 702. When basket 701 is attached to the bottom of stirring shaft 702, the bottom of lower disk 901 of cap plug 900 rests on top of basket 701. Assuming that vessel cover 800 is positioned in opening 107 of FIG. 7 and that basket 701 and cap plug 900 are positioned above vessel cover 800, the following describes what happens as basket 701 is lowered into vessel 101. As basket 701 is lowered through opening 801, upper disk 902 of cap plug 900 comes to rest atop cover 800, with lower disk 901 resting substantially inside central opening 801. Basket 701 continues to be lowered until basket 701 is submerged in solution 103. The combination of cover 800 and cap plug 900 then provide evaporation prevention and contamination-probability minimization for dissolution-testing module 700. Basket 701 may then be raised while leaving cover 800 in place, whereupon cap plug 900 is subsequently lifted with basket 701 and rests atop basket 701.